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심혈관 보호작용

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  • 2019-02-21 10:56:00
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1 심장, 심 혈관 보호작용
울혈성 심장질환과 심근 허혈 ,혈전용해,혈관 확장 작용
1) "Forty-five patients with class IV cardiac function were divided into three groups of 15: group I (digoxin group), group II (Red Ginseng group) and group III (Red Ginseng plus digoxin group). After treatment, the improvement of the hemodynamical and biochemical indexes of group II and group III were greater than those of group I, and group III was the most significant amongst all. The results suggested that Red Ginseng and digoxin had synergism for treatment of congestive heart failure, and Red Ginseng was an effective and safe adjuvant without any side effects.
      Class4의 심장기능부전환자 45명을 15명씩3군으로 나눠 1군은 digoxin,2군은 홍삼,3군은 Digoxin+홍삼으로 투여 후 혈액동력학적 및 생화학적 개선치는 2군과 3군에이 1군에 비해 훨씬 좋았으며 특히 3군이 그중 가장 좋았다. 이 결과는 홍삼과 Digoxin이 울혈성 심장질환의 치료에 상승작용이 있고 홍삼이 효과적이고 부작용 없는 안전한 보조약제로 보인다.
2)"Thirty mistrals valvular surgical patients were randomly divided into three groups for study of protective effects of Ginsenoside on myocardiac ischemic and reperfusion injuries We conclude that both Ginsenoside in total and Ginsenoside Rb have protectiveeffects on myocardiac ischemic and reperfusion injuries in open heartsurgery, and the effect of Ginsenoside in total is even better than that of Ginsenoside Rb.
     30명의 판막 수술환자를 임의로 3군으로 나눠 진세노사이드가 심근 허혈 및 reperfusion 상처에 대한 방어 효과를 조사하였다. 진세노사이드와 Rb는 심장개복수술에서 심근 허혈과 reperfusion 상처에 방어적 효과가 있고 총 진세노사이드가 Rb보다 더 효과적이라고 결론지었다.
3). The effects of various ginseng saponins isolated from red ginseng roots, on aggregation and 5-hydroxytryptamine release (5-HT) human platelets have been investigated The results suggest that ginsenoside Rg1 in red ginseng roots may be active as a drug in the treatment of atherosclerosis and thrombosis. 
      홍삼 근으로부터 분리한 다양한 사포닌의 5-HT 방출 인간 혈소판과 응집에 대한 효과를 연구하였다. Rg1이 동맥경화와 혈전 증 치료에 활성이 있다고 추측된다.
4) "studied the effectof dietary supplementation of a lipophilic fraction from Panax ginseng on rat platelet aggregation and blood coagulationfound that the level of lipids s.c. as triglyceride, total cholesterol, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol was decreased in serum suggesting that dietary LF regulates the levels of cGMP and cAMP. Accordingly, our data demonstrate that dietary LF has an antithrombotic effect in vivo.
      고려인삼의 지질용해성분획(LF)의 섭취가 쥐의 혈청 응집 및 혈액 응고에 대한 효과 연구에서 TG,총  고밀도 지단백 콜레스테롤과 저밀도지단백콜레스테롤이 혈청에서 낮아지는 것은 LF가 cGMP와cAMP를 조절하는 것이 아닌 가 추측하게하며 우리의 데이터에 의하면 LF의 섭취는 생체 내에서 antithrombotic effect가 있다.
1. Clin Exp Pharmacol Physiol. 1996 Aug;23(8):728-32.
Cardiovascular protection by ginsenosides and their nitric oxide releasing action.
Chen X.Department of Pharmacology, Human Medical University, Changsha, China.
1. In an animal model in vivo, ginsenosides (GS), saponins from Panax ginseng, were shown to protect against myocardial ischaemia/reperfusion damage with concomitant increased 6-keto-PGF1 alpha and decreased lipid peroxidation.2. In perfused rabbit lung in situ and isolated rabbit aortic rings, GS protected the pulmonary and aortic endothelium against electrolysis-induced free radical injury. Purified components of GS, Rb1 and especially Rg1, relaxed pulmonary vessels and this effect was eliminated by nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase. 3. In cultured bovine aortic endothelial cells, GS enhanced the conversion of [14C]-L-arginine to [14C]-L-citrulline, indicating an increased release of NO. 4. As the neurotransmitter inducing penile erection, NO release was shown to be enhanced by GS in rabbit corpus cavernosum (CC) in vitro. Ginsenosides enhanced both acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cGMP. The latter effect was eliminated by tetrodotoxin and was associated with decreased tissue cGMP. Ginsenoside-enhanced CC relaxation was attenuated by nitro-L-arginine and oxyhaemoglobin, and enhanced by superoxide dismutase. 5. It is postulated that cardiovascular protection by GS may be partly mediated by the release of NO, a potent antioxidant, and that the GS-enhanced release of NO from endothelial cells, especially from perivascular nitric oxidergic nerves in the CC, may partly account for the aphrodisiac effect of Panax ginseng used in traditional Chinese medicine. 
진세노사이드의 심 혈관 보호 작용과 NO방출작용
1.생체 내 동물실험에서 고려인삼의 진세노사이드는 increased 6-keto-PGF1 alpha 를 증가시키고 지방 과산화를 감소시키는 방식으로 심근 허혈/재 관류 손상으로부터 보호한다.
2.환류된 토끼의 폐와 분리된 대동맥에서 진세노사이드는 전기로 유도된 자유기 손상으로부터 대동맥 및 폐동맥 상피세포를 보호한다. 순수한 진세노사이드 성분인 Rb1과 Rg1은 폐동맥을 이완시키는데 이 효과는 nitro-L-arginine( NO합성의 억제제)에 의해 소실된다.
3.배양된 소의 대동맥 상피세포에서 진세노사이드는 L-arginine을 L-citrulline로 전환하는 것을 강화하는데 이는 NO의 방출을 의미한다.
4.실험관내 실험을 통해 토끼의 해면체에서 진세노사이드는 발기를 유도하는 신경전달물질로서  NO의 방출이 강화된 것을 보여준다.진세노사이드는 조직 내 c-GMP의 증가로 추정되는 이완활성의 신경 촉진 및 아세칠콜린 유도를 강화한다. 이완 활성은 tetrodotoxin로 소실되는데 이는조직 내  cGMP.의 감소로 추정된다. 진세노사이드의 해면체 이완 강화작용은 nitro-L-arginine and oxyhaemoglobin로 감소하고 활성산소 청소효소에 의해 강화된다.
5. 심 혈관 보호 작용은 항산화제인  NO의 방출로 일어나며 진세노사이드는 상피세포로부터 NO유출을 강화하여 심 혈관을 보호하는데 특히 해면체의 혈관주위 NO생성 신경세포로부터 NO의 방출 강화는 전통적 한의학에서 인삼을 최음제로 사용하는 효과를 설명하는 것이다.:PMID: 8886498 [PubMed - indexed for MEDLINE]
2.Am J Chin Med. 1992;20(2):167-73.
Inhibitory effect of ginsenosides on migration of arterial smooth muscle cells.
Koyama N, Morisaki N, Saito Y, Yoshida S.Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Migration of arterial smooth muscle cells (SMC) in the arterial wall plays an important role in the formation of intimal thickening of atherosclerotic lesions. In this study, we examined the effect of ginsenosides on SMC migration induced by platelet-derived growth factor (PDGF) and SMC-derived migration factor (SDMF). Ginsenosides had inhibitory effects on SMC migration and the striking effects were observed with ginsenoside-Rb2 and -Rc in a dose-dependent manner. These results suggest that the administration of ginsenosides on the patients may prevent intimal thickening, in part, by inhibiting SMC migration in the arterial wall.
진세노사이드의 동맥평활 근 세포 이동 억제 효과
동맥 평활 근 세포의 이동은(SMC) 동맥경화증 부위에서 두꺼워지는 것에  중요한 역할을 한다.
이 연구에서는 진세노사이드가 혈소판유래 성장인자(PDGF)와  SMC유래이동인자(SDMF) 유도된 에 대한SMC이동의 효과를 시험하였다. 진세노사이드는 SMC이동에 억제적 효과가 있고 Rb2,Rc에서 용량 의존적으로  .striking 효과가 관찰 되었다.이들 결과는 환자에게 진세노사이드의 투여가 동맥  벽에서 SMC의 이동을 억제하여 intimal 두께를 예방 할 것으로 추측된다.
 PMID: 1519557 [PubMed - indexed for MEDLINE]

3.nghua Yi Xue Za Zhi. 1994 Oct;74(10):626-8, 648.
[Protective effects of ginsenoside on myocardiac ischemic and reperfusion injuries]
[Article in Chinese]Zhan Y, Xu XH, Jiang YP.Department of Cardiothoracic Surgery, Second Affiliated Hospital, Hunan Medical University, Changsha.

Thirtymitral valvular surgical patients were randomly divided into three groups for study of protective effects of Ginsenoside on myocardiac ischemic and reperfusion injuries. In GI, 11 patients (controls), no Ginsenoside was used, in GII, 11, Ginsenoside in total was added into the cardioplegic solusion made in our hospital, and in GIII, 8, instead of Ginsenoside in total Ginsenoside Rb was added. During operation comparative studies were made of pre- and postoperative cardiac functions with intraoperative transesophageal echocardiography and ultrastructures of myocardiac cells with electromicroscopy. We conclude that both Ginsenoside in total and Ginsenoside Rb have protective effects on myocardiac ischemic and reperfusion injuries in open heart surgery, and the effect of Ginsenoside in total is even better than that of Ginsenoside Rb.Publication Types:Trial Randomized Controlled Trial PMID: 7842343 [PubMed - indexed for MEDLINE]
4. Zhongguo Zhong Yao Za Zhi. 2001 Jun;26(6):416-9.
[Protective effect of Panax quinquefolium 20s-proto-panaxdiolsaponins on acute myocardial infarction in dogs
Sui DY, Yu XF, Qu SC, Lu ZZ, Wang L, Chen MQ.Department of Pharmacology, Bethune Medical University, Changchun 130021, Jilin, China.
OBJECTIVE: To study the protective effects of Panax quinquefolium 20s-protopanaxdiolsaponins extracted from leaves of P. quinquefolium (PQDS) on acute myocardial infarction(AMI) in dogs. 

METHOD: The parameters of myocardial infarct size, the serum CK and LDH activity, myocardial metabolism, free radicals and coronary circulation etc were determined by using the model of ligation of LAD in the anaesthetized open-chest dogs. RESULT: In dogs treated with PQDS(in a dosage of 10 and 20 mg.kg-1 i.v. infusion), the myocardial infarct size, the activity of serum CK, LDH and the contents of serum FFA and LPO were decreased, whereas the activity of serumSOD and GSH-Px increased markedly. At the same time, myocardial blood flow was increased and coronary vascular resistance decreased significantly. CONCLUSION: PQDS has protective effect on myocardial ischemia by modifying metabolic dysfunction of FFA, inhibiting oxygen free radical mediated peroxidation of membrane lipids, enhancing endogenous antioxidase activity and increasing myocardial blood supply.
개에게서 미국 삼 20S-PPD사포닌의 급성 심근 경색에 대한 방어적 효과
목적:  개를 대상으로 미국 삼의 잎에서 투출한 20S-PPD사포닌이 급성 심근 경색에 대한 방어적 효과를 연구하기 위함
방법: 심근 경색의 크기 지표인 혈청 CK,와 LDH활동, 심근 대사, 자유기와 동맥 순환 등이 미취되어 가슴을 절개한 개에 있어 LAD의 결찰 모델을 사용하여 검토되었다. 결과:POD로 처리한(in a dosage of 10 and 20 mg.kg-1 i.v. infusion)개에 있어 심근 경색 크기와 혈청 CK,LDH와 혈청 FFA와 LPO는 감소한 반면 혈청 SOD와 GSH-Px 는 현저히 증가하였다. 동시에 심근 혈액 흐름은 증가하였고 관상동맥 저항성은 의미 있게 감소하였다. 
결론:PODS는 FFA의 대사적 기능부전을 바꿔  세포막 지질의 과산화를 매개하는 자유산소기를 억제하고 상피세포의 항산화제 활동을 강화하고 심근 혈액 공급을 증가시켜 심근 허혈에 방어적 효과를 지닌다.
5. Acta Pharmacol Sin. 2003 Feb;24(2):102-8.
Enhancement of fibrinolytic activity of bovine aortic endothelial cells by ginsenoside Rb2 
.Liu JW, Wei DZ, Du CB, Zhong JJ.state Key Laboratory of Bioreactor Engineering, Institute of Biochemistry, East China University of Science and Technology, Shanghai 200237, China 

AIM: The effect of ginsenoside Rb2 purified from Panax ginseng on fibrinolytic activity of bovine aortic endothelial cells (BAEC) was investigated. METHODS: Cellular plasminogen activator (PA) level of the lysates was measured by the chromogenic substrate S-2403. Fibrin underlay technique was carried out to observe fibrinolysis by growing endothelial cells in the culture medium. Cell viability was then determined by measurement of the activity of mitochondrial dehydrogenase. The ability of Rb2 of potentiating cellular PA activity was investigated by measuring the amounts of PA and PA inhibitor-1 (PAI-1) in the culture medium using zymography and reverse zymography. Changes in the expression of urokinase-type PA (uPA), uPA receptor, and PAI-1 mRNA in BAEC after treatment with Rb2 were analyzed by Northern blot. RESULTS: Rb2 enhanced cellular PA activity in a concentration-and time-dependent manner. Treatment of BAEC with Rb2 10 mg/L for 9 h resulted in a 3.5-fold increase of PA activity without a marked cytotoxic effect, as shown by LDH levels in culture. Increased PA levels caused the increase in surface plasmin levels as observed by fibrin underlay technique. Rb2 greatly or moderately increased the amount of urokinase-type PA (uPA) or its inhibitor (PAI-1), present in the culture medium, whereas saponin did not influence mRNA levels of uPA, its surface receptor, and PAI-1, suggesting that Rb2 may stimulate the secretion of uPA without enhancing its gene expression.The enhancement of PA levels by retinoic acid alone, a stimulator of PA synthesis, was potentiated by the simultaneous addition of ginsenoside Rb2 1 mg/L. Therefore, Rb2 might exert a strong synergism in the synthesis of cellular PA in BAEC. CONCLUSION: Ginsenoside Rb2 enhanced the PA activity levels in BAEC as well as the surface plasmin activity of BAEC. Rb2 may stimulate the secretion of uPA without enhancing the gene expression of uPA, uPA receptor (uPAR), and PAI-1.
Rb2는 소의 동맥내피세포에서 프라스미노겐 활성화 인자를 활성화하여 혈전용해작용을 한다


6.Br J Pharmacol. 2003 Oct;140(4):661-70.
Ginsenoside Rg3 inhibits phenylephrine-induced vascular contraction through induction of nitric oxide synthase.
Kim ND, Kim EM, Kang KW, Cho MK, Choi SY, Kim SG.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Sillim-dong, Kwanak-gu, Seoul 151-742, South Korea. ndk@snu.ac.kr

Ginsenoside Rg3 (Rg3) isolated from Panax ginseng relaxes vessels and exerts a cytoprotectiveeffect. In view of the fact that nitric oxide (NO) is involved in vascular hyporeactivity and immunostimulation, the effects of total ginsenosides (GS) and Rg3 on the vascular responses and the expression of inducible nitric oxide synthase (iNOS) were investigated. Vasocontraction of endothelium-denuded aortic ring was induced by phenylephrine with or without GS or Rg3. The expression of iNOS was assessed by Western blot and RT-PCR analyses. NF-kappaB activation was monitored by gel shift, immunoblot and immunocytochemical analyses. Incubation of the endothelium-denuded aortic ring with GS or Rg3 inhibited phenylephrine-induced vasocontraction, which was abrogated by NOS inhibition. GS or Rg3 increased NO production in aortic rings, but Rb1, Rc, Re and Rg1 had no effect. Aortic rings obtained from rats treated with GS or Rg3 responded to phenylnephrine to a lesser extent, while producing NO to a larger extent, than those from control animals. GS or Rg3 induced iNOS in vascular smooth muscle. Rg3 induced iNOSwith increase in NO production in Raw264.7 cells. Rg3 increased NF-kappaB DNA binding, whose band was supershifted with anti-p65 and anti-p50 antibodies, and elicited p65 nuclear translocation, which was accompanied by phosphorylation and degradation of I-kappaBalpha. PKC regulated iNOS induction by Rg3. In conclusion, Rg3 relaxes vessels as a consequence of NO production, to which iNOS induction contributes, and iNOS induction by Rg3 accompanied NF-kappaB activation, which involves phosphorylation and degradation of I-kappaBalpha and nuclear translocation of p65.PMID: 14534150 [PubMed - in process]
Rg3는 No의 생산을 지속적으로 하여 혈관을 이완 시키나 Rb1,Rc,Re,Rg1은 효과가 없다

7.Wu Xue Bao. 1999 Dec;32(4):349-52.
Effects of ginsenosides on myocardial reperfusion arrhythmia and lipid superoxidation in high cholesterol diet rats.
Yang Y, He K, Wu T, Li Q, Zhang JS, Fu ZG.
Department of Pharmacology, Guangdong Medical College, Zhanjiang 524023.

To explore the effects of GSL on myocardial reperfusion arrhythmia and lipid superoxidation in high cholesterol diet rats. Hyperlipidemia model was set up with administered high cholesterol emulsion 15 ml/kg to rats orally for 14 days. In GSL group, rats were given GSL i.p. 75 mg/kg simultaneously when administered high cholesterol emulsion. The experiment of myocardial ischemia reperfusion was performed on all rats. The results showed: (1) After administration of high cholesterol emulsion to rats orally for 14 days, hyperlipidemia model was set up successfully, simultaneously treatment with GSL. It lowered serum lipid; (2) In hyperlipidemia state, serum MDA increased (p < 0.01, SOD and NO decreased markedly (p < 0.01 and p < 0.05 respectively) after 2 h of myocardial reperfusion; the rate of reperfusion arrhythmia (RPAr) increased within 10 min of reperfusion, four out of nine rats died of ventricular fibrillation (VF); and (3) GSL decreased MDA, increased SOD and NO after 2 h of myocardial reperfusion. All changes were significant (p < 0.01); the rate of RPAr decreased, no VF occurred and all rats survived. Hyperlipidemia aggravated myocardial ischemia reperfusion injury and increased the incidence of RPAr. The results suggested that GSL reduced myocardial ischemia reperfusion injury and RPAr in high cholesterol diet state through antiperoxidating and inducing the production of NO.
PMID: 12548861 [PubMed - indexed for MEDLINE] 

8.J Huazhong Univ Sci Technolog Med Sci. 2002;22(3):212-5.
Effect of ginsenoside-Rb1 on cardiomyocyte apoptosis after ischemia and reperfusion in rats.
Guan L, Li W, Liu Z.Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.
The effect of ginsenoside Rb1 on cardiomyocyte apoptosis after ischemia (30 min) and reperfusion (6 h) in rats was observed. The ischemia/reperfusion heart model was established by ligating left anterior descending branch of coronary artery in Wistar rats. The apoptotic cardiomyocytes were examined under transmission electron microscopy and counted by in situ nick end labeling (TUNEL) method and light microscopy. Results showed that (1) The apoptotic cardiomyocytes were found in ischemic regions in the ischemia/reperfusion group, but not in the sham-operating group under transmission electron microscopy; (2) The number of apoptotic cells were 134.45 +/- 45.61/field in the ischemia/reperfusion group, 0/field in the sham-operating group and 51.65 +/- 13.71/field in the ginsenoside Rb1-treated group. The differences were significant among the three groups (P < 0.01). It was concluded that myocardial ischemia-reperfusion could induce cardiomyocyte apoptosis, and ginsenosideRb1 could significantly inhibit cardiomyocyte apoptosis induced by ischemia-reperfusion in rats, indicating that ginsenoside Rb1 could inhibit cardiomyocyte apoptosis induced by ischemia-reperfusion, thus alleviating ischemia-reperfusion injury.
PMID: 12658806 [PubMed - indexed for MEDLINE] 






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